We are evaluating biomarkers in patients with severe infections that lead to shock and lung dysfunction. Samples are being analyzed in collaboration with collaborators at the University of Tennessee Memphis who have conducted a trial prospectively evaluating the effects of corticosteroids on outcome from septic shock or severe respiratory failure. Our goals are to evaluate biomarkers at the time of study entry and during the course of the illness to determine if there are molecules that will help characterize the patients who are likely to have a beneficial response from corticosteroid therapy. During the last year we have screened samples from patients with documented infection and ARDS for chemokines, cytokines, hemostatic, and growth factors that have been suggested to play a role in the pathogenesis of lung injury. We utilized a highly sensitive antibody profiling technology to study autoantibodies in 48 patients with either acute respiratory distress syndrome (ARDS) or severe sepsis. 57% of ARDS and 46% of septic patients without ARDS had elevated autoantibodies compared to the healthy controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that titers of low autoantibodies at early time points rose precipitously and peaked between days 7-14. The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self-proteins and may contribute to late term sequela of systemic inflammation. We studied biomarkers in 79 patients receiving methylprednisolone or usual care during early ARDS. Interleukin-6, tumor necrosis factor &#945;, vascular endothelial growth factor, protein C, procalcitonin and proadrenomedullin were measured in archived plasma. We found that the changes in biomarkers changes varied with the precipitating cause of ARDS (infectious vs noninfectious and pulmonary vs non-pulmonary etiologies), suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of ARDS.